Bone & Soft Tissue Tumours
Pathology · Neoplasia · lean revision notes
Bone & Soft Tissue Tumours
Bone and soft tissue tumours are a favourite NEET PG topic because each entity carries a near-pathognomonic triad — a typical age, a typical site, and a typical radiology–histology signature. Master those triads and the cytogenetics, and you can crack most stems on sight.
Quick orientation
The single highest-yield mental model: age + location + X-ray pattern → diagnosis. Bone-forming tumours make osteoid (osteosarcoma), cartilage-forming tumours make chondroid matrix (chondroma, chondrosarcoma), and "small round blue cell" tumours (Ewing) make neither. Soft tissue sarcomas are classified by line of differentiation (fat, muscle, fibrous, vascular).
High-yield: The two commonest primary malignant bone tumours overall are osteosarcoma (1st) and chondrosarcoma (2nd); multiple myeloma is the commonest malignant tumour involving bone if marrow tumours are counted. Metastasis is the commonest malignant lesion of bone overall.
Classification of bone tumours
| Tissue of origin | Benign | Malignant |
|---|---|---|
| Bone (osteoid) | Osteoid osteoma, osteoblastoma, osteoma | Osteosarcoma |
| Cartilage | Osteochondroma, enchondroma, chondroblastoma, chondromyxoid fibroma | Chondrosarcoma |
| Unknown / round cell | — | Ewing sarcoma, primary lymphoma of bone |
| Fibrous | Non-ossifying fibroma, fibrous dysplasia | Fibrosarcoma, MFH/UPS |
| Giant cell rich | Giant cell tumour (locally aggressive) | Malignant GCT (rare) |
| Notochord | — | Chordoma |
High-yield: Osteochondroma (exostosis) is the commonest benign bone tumour; osteosarcoma is the commonest primary malignant bone tumour. Multiple hereditary exostoses (EXT1/EXT2 genes) carry a small risk of chondrosarcomatous transformation.
Osteosarcoma
Epidemiology & pathophysiology
- Bimodal age: primary peak in adolescents (10–20 yrs, during the growth spurt); second peak >60 yrs (secondary, on a background of Paget disease, prior radiation, or bone infarct).
- Site: metaphysis of long bones around the knee — distal femur > proximal tibia > proximal humerus. This is the "knee away, elbow toward" rule for tumour distribution around the most active growth plates.
- Genetics: inactivation of RB1 (also explains osteosarcoma risk in hereditary retinoblastoma) and TP53 (germline mutation → Li–Fraumeni syndrome). MDM2/CDK4 amplification in parosteal variants.
Clinical features
- Painful, enlarging deep-seated mass; often presents after trivial trauma drawing attention to it.
- Raised serum alkaline phosphatase (ALP) and LDH — used for prognosis/monitoring.
- Spreads haematogenously to lungs (commonest metastatic site); "skip lesions" within the same bone.
Radiology
- Codman triangle: periosteum lifted off the cortex by the tumour, ossifying at the angle.
- Sunburst / sunray appearance: spiculated new bone perpendicular to the cortex.
- Mixed lytic–sclerotic lesion with cortical destruction and soft-tissue extension.
Histology
- Malignant osteoblasts producing lacy osteoid (the defining feature — any osteoid produced by frankly malignant cells = osteosarcoma).
- Marked pleomorphism, atypical mitoses.
- Variants: conventional (intramedullary, high-grade), parosteal (surface, low-grade, better prognosis), periosteal, telangiectatic (lytic, aggressive).
High-yield: Osteoid laid down by anaplastic malignant cells is the diagnostic hallmark of osteosarcoma. Codman triangle and sunburst are radiological, not pathognomonic histology.
Management
Diagnosis → neoadjuvant chemotherapy → limb-salvage surgery (or amputation) → adjuvant chemotherapy.
- Chemotherapy regimen: MAP — high-dose Methotrexate (with leucovorin rescue), Adriamycin (doxorubicin), Platinum (cisplatin).
- >90% tumour necrosis on the resected specimen after neoadjuvant chemo is the best prognostic marker.
- 5-year survival ~60–70% with localised disease; falls sharply with lung metastases.
Ewing sarcoma
The classic "small round blue cell tumour" of bone — the most heavily tested cytogenetic entity in this chapter.
Key facts
- Age: children & adolescents (5–20 yrs); slightly younger than osteosarcoma.
- Site: diaphysis / metaphysis of long bones (femur) and flat bones (pelvis, ribs). Note: osteosarcoma = metaphysis; Ewing = often diaphysis.
- Genetics: t(11;22)(q24;q12) → EWSR1–FLI1 fusion gene (member of the EWS-ETS family). This translocation is the single most repeated NEET PG fact for Ewing.
- Part of the PNET / Ewing family of tumours; shares neuroectodermal differentiation.
Clinical & lab
- Painful enlarging mass; may have fever, raised ESR, leucocytosis → mimics osteomyelitis (important differential).
- Onion-peel periosteal reaction on X-ray.
Radiology
- "Onion-skin" (laminated) periosteal reaction — concentric layers of reactive bone. (Codman triangle can also occur.)
- Permeative, "moth-eaten" lytic lesion of the diaphysis.
Histology & IHC
- Sheets of uniform small round blue cells with scant cytoplasm; Homer-Wright rosettes may be seen (neural differentiation).
- PAS positive (cytoplasmic glycogen); diastase-labile.
- IHC: CD99 (MIC2) membranous positivity, FLI-1 positive.
Management
- Highly chemosensitive and radiosensitive: multi-agent chemo (VAC/IE — vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide) + local control by surgery and/or radiotherapy.
High-yield: Ewing = t(11;22), EWSR1–FLI1, CD99+, PAS+ glycogen, onion-skin periosteal reaction, Homer-Wright rosettes. Memorise this constellation verbatim.
Small round blue cell tumours — the differential
A perennial integration question. Use this comparison table.
| Tumour | Marker / clue | Genetics |
|---|---|---|
| Ewing sarcoma / PNET | CD99+, PAS+ glycogen | t(11;22) EWSR1-FLI1 |
| Neuroblastoma | NSE+, ↑urinary VMA/HVA, Homer-Wright rosettes | MYCN amplification |
| Rhabdomyosarcoma | Desmin, myogenin, MyoD1 | t(2;13) PAX3-FOXO1 (alveolar) |
| Lymphoma/leukaemia | LCA (CD45)+, TdT | varies |
| Small cell osteosarcoma | osteoid production | — |
| Wilms tumour | WT1+ | WT1 (11p13) |
Chondrosarcoma
- Second commonest primary malignant bone tumour; tumour of older adults (40–60 yrs), unlike osteosarcoma/Ewing.
- Site: central skeleton — pelvis, proximal femur, shoulder girdle, ribs.
- Produces malignant cartilage (chondroid) matrix; no osteoid.
- Histology: increased cellularity, binucleate chondrocytes, plump nuclei in lacunae; graded I–III (grade predicts behaviour).
- May arise de novo or secondarily from a pre-existing osteochondroma/enchondroma.
- Relatively chemo- and radio-resistant → wide surgical excision is the mainstay.
High-yield: Chondrosarcoma in an older adult, axial/proximal location, with chondroid matrix that is resistant to chemo/radiotherapy → surgery is treatment of choice. Contrast with the chemosensitive osteosarcoma/Ewing of the young.
Giant Cell Tumour of bone (Osteoclastoma)
- Age: 20–40 yrs (after physeal closure) — the key discriminator from other tumours which are commoner in the immature skeleton.
- Site: epiphysis extending to metaphysis of long bones, classically the distal femur / proximal tibia (around the knee) and distal radius.
- Radiology: eccentric, "soap-bubble" / lytic lesion reaching up to the subchondral bone, often with a narrow zone of transition.
- Histology: numerous multinucleated osteoclast-type giant cells evenly distributed among mononuclear stromal cells (the neoplastic component — express RANKL).
- Behaviour: locally aggressive, benign but high recurrence; ~1–2% metastasise to lung ("benign metastasising").
- Management: extended curettage with adjuvant (phenol/PMMA cement) or wide excision; denosumab (anti-RANKL) for unresectable/recurrent disease.
High-yield: GCT = epiphyseal, 20–40 yrs, soap-bubble lytic lesion, osteoclast giant cells, RANKL-driven, treat with denosumab. Giant cells are reactive; the mononuclear stromal cell is neoplastic.
Differential of giant-cell–rich lesions
Brown tumour of hyperparathyroidism, aneurysmal bone cyst, chondroblastoma, non-ossifying fibroma, giant cell reparative granuloma.
Benign bone tumours worth a line each
| Tumour | Age/Site | Signature |
|---|---|---|
| Osteoid osteoma | Young, long bone cortex | Night pain relieved by NSAIDs/aspirin, radiolucent nidus <1.5 cm, ↑PGE2 |
| Osteoblastoma | Spine | Like osteoid osteoma but >2 cm, pain not relieved by aspirin |
| Osteochondroma | Metaphysis, away from joint | Cartilage-capped bony exostosis, commonest benign tumour |
| Enchondroma | Small bones of hand | O-ring/ stippled calcification; Ollier disease, Maffucci syndrome (with haemangiomas) |
| Chondroblastoma | Epiphysis, young | "Chicken-wire" calcification |
| Fibrous dysplasia | — | GNAS mutation, "ground-glass" matrix; with café-au-lait + precocious puberty = McCune–Albright |
High-yield: Osteoid osteoma → severe night pain dramatically relieved by NSAIDs; small radiolucent nidus. Classic single-best-answer.
Soft tissue tumours
Soft tissue sarcomas are classified by line of differentiation. The two NEET-relevant ones here are rhabdomyosarcoma (children) and liposarcoma (adults).
Rhabdomyosarcoma (RMS)
- Commonest soft tissue sarcoma in children; skeletal-muscle differentiation.
- Subtypes:
- Embryonal — commonest overall; head & neck, genitourinary. Sarcoma botryoides = polypoid "bunch of grapes" variant in vagina/bladder of infants.
- Alveolar — adolescents, extremities; t(2;13) PAX3-FOXO1 (or t(1;13) PAX7-FOXO1); worse prognosis.
- Pleomorphic — adults.
- Histology: rhabdomyoblasts with eccentric eosinophilic cytoplasm; strap/tadpole cells with cross-striations.
- IHC: desmin, myogenin, MyoD1 positive.
High-yield: RMS — childhood, desmin/myogenin/MyoD1+; embryonal botryoides in GU tract; alveolar = t(2;13) PAX3-FOXO1.
Liposarcoma
- One of the commonest soft tissue sarcomas of adults (40–60 yrs); deep soft tissue of thigh and retroperitoneum.
- Hallmark cell: the lipoblast — atypical cell with cytoplasmic vacuoles scalloping the nucleus.
- Well-differentiated/dedifferentiated types: MDM2 & CDK4 amplification (ring chromosomes); myxoid liposarcoma: t(12;16) FUS-DDIT3 (CHOP).
- Myxoid type has a "chicken-wire" capillary vasculature; pleomorphic type is most aggressive.
Cytogenetics cheat-sheet (frequently tested)
| Tumour | Translocation | Fusion gene |
|---|---|---|
| Ewing sarcoma / PNET | t(11;22)(q24;q12) | EWSR1-FLI1 |
| Alveolar rhabdomyosarcoma | t(2;13)(q35;q14) | PAX3-FOXO1 |
| Myxoid liposarcoma | t(12;16)(q13;p11) | FUS-DDIT3 (CHOP) |
| Synovial sarcoma | t(X;18)(p11;q11) | SS18-SSX |
| Clear cell sarcoma | t(12;22) | EWSR1-ATF1 |
| Dermatofibrosarcoma protuberans | t(17;22) | COL1A1-PDGFB |
| Desmoplastic small round cell tumour | t(11;22) | EWSR1-WT1 |
High-yield: Synovial sarcoma (despite the name, rarely intra-articular; young adults, near joints) → t(X;18), SS18-SSX, biphasic spindle + epithelial pattern, TLE1+.
Approach to a bone-tumour stem
1. Note the age → child/adolescent suggests osteosarcoma or Ewing; 20–40 yrs suggests GCT; >40 yrs suggests chondrosarcoma/metastasis/myeloma. 2. Note the site → epiphysis (GCT, chondroblastoma); metaphysis (osteosarcoma); diaphysis (Ewing); axial (chondrosarcoma). 3. Read the X-ray pattern → sunburst/Codman (osteosarcoma); onion-skin (Ewing); soap-bubble lytic (GCT); nidus (osteoid osteoma). 4. Read the histology/IHC → osteoid (osteosarcoma); CD99+ blue cells (Ewing); osteoclast giant cells (GCT); chondroid (chondrosarcoma); lipoblast (liposarcoma). 5. Confirm with cytogenetics when offered.
Site mnemonic
"Epiphysis = **GCT/Chondroblastoma; Metaphysis = osteosarcoma; Diaphysis = Ewing" → think E-M-D.
Key differentials & traps
| Confusion | Discriminator |
|---|---|
| Ewing vs osteomyelitis | Both: fever, ↑ESR, lytic bone, onion-skin. Biopsy: blue cells, CD99+ |
| Osteosarcoma vs Ewing | Osteoid + sunburst + metaphysis (OS) vs blue cells + onion-skin + diaphysis (Ewing) |
| GCT vs aneurysmal bone cyst | Solid stromal cells with even giant cells (GCT) vs blood-filled spaces |
| Chondrosarcoma vs enchondroma | Older age, axial site, cellularity, pain, cortical destruction → malignant |
| Brown tumour vs GCT | Check serum Ca²⁺/PTH — hyperparathyroidism |
Recently asked / exam angle
- Ewing sarcoma translocation — answer t(11;22) EWSR1-FLI1 — is one of the most repeated single-best-answer items in pathology.
- CD99 (MIC2) positivity and PAS-positive (glycogen) small round blue cells → Ewing. PAS positivity that is diastase-labile confirms glycogen.
- Image-based: Codman triangle / sunburst photo → osteosarcoma; onion-skin → Ewing; soap-bubble epiphyseal lytic lesion → GCT.
- Osteosarcoma genetics: RB1 and TP53; link to Li–Fraumeni and hereditary retinoblastoma.
- Denosumab (anti-RANKL) as treatment of giant cell tumour — newer favourite.
- Best prognostic factor in osteosarcoma = percentage tumour necrosis after neoadjuvant chemotherapy (≥90% = good).
- Alveolar RMS = t(2;13) PAX3-FOXO1; myxoid liposarcoma = t(12;16) FUS-DDIT3; synovial sarcoma = t(X;18).
- Commonest malignant bone tumour overall = metastasis; commonest primary = osteosarcoma; 2nd primary = chondrosarcoma.
- Osteoid osteoma: night pain relieved by NSAIDs, radiolucent nidus, ↑prostaglandins.
- IHC integration: desmin/myogenin (rhabdomyo), CD99 (Ewing), MDM2/CDK4 (liposarcoma/parosteal osteosarcoma), TLE1 (synovial sarcoma).
Rapid revision
- Osteosarcoma: 10–20 yrs, metaphysis around knee, Codman triangle + sunburst, malignant osteoid, RB1/TP53, lung mets, MAP chemo.
- Ewing sarcoma: 5–20 yrs, diaphysis, onion-skin, small round blue cells, CD99+, PAS+ glycogen, t(11;22) EWSR1-FLI1.
- Chondrosarcoma: older adults, axial skeleton, chondroid matrix, chemo/radio-resistant → surgery.
- GCT (osteoclastoma): 20–40 yrs, epiphysis, soap-bubble lytic, osteoclast giant cells + neoplastic stromal cells (RANKL), denosumab.
- Osteochondroma = commonest benign bone tumour (cartilage-capped exostosis, EXT1/2).
- Osteoid osteoma = night pain relieved by NSAIDs, nidus <1.5 cm, ↑PGE2.
- Best osteosarcoma prognostic factor = ≥90% tumour necrosis post-neoadjuvant chemo.
- Rhabdomyosarcoma = commonest childhood soft tissue sarcoma; desmin/myogenin/MyoD1+; embryonal botryoides (GU), alveolar t(2;13).
- Liposarcoma = commonest adult soft tissue sarcoma; lipoblast; myxoid t(12;16) FUS-DDIT3.
- Synovial sarcoma = t(X;18) SS18-SSX, biphasic, TLE1+, young adults near joints.
- Site rule: Epiphysis = GCT/chondroblastoma; Metaphysis = osteosarcoma; Diaphysis = Ewing.
- Metastasis is the commonest malignant bone lesion overall; multiple myeloma is the commonest primary marrow malignancy involving bone.